Metabolic diseases such as type 2 diabetes (T2D), obesity and their related co-morbidities have reached epidemic proportions worldwide. While progress continues to be made into the molecular mechanisms involved in both obesity and T2D, the identification and development of safe, efficacious therapeutic modalities is significantly limited. There is an urgent need for innovative medicines to combat both obesity and diabetes. Recent data along with our preliminary data strongly suggest that pharmacological intervention of Fyn kinase provides an excellent target and novel approach for the discovery of new drugs to treat metabolic disease. In preliminary high throughput screens we have identified a promising selective inhibitor of Fyn kinase. This proposal describes an approach for further development and identification of additional analogs of our lead compound. This will include SAR based on novel chemistries, characterization in human cell-based assays for glucose and fatty acid metabolism as well as biochemical assays centered on potential mechanism of action. PUBLIC HEALTH RELEVANCE: Metabolic diseases such as type 2 diabetes, obesity and their related co-morbidities have reached epidemic proportions worldwide. There is an urgent need for innovative medicines to combat both obesity and diabetes. This proposal focuses on further development and identification of lead small molecule drug for the treatment of metabolic disease.